Malignant melanoma (MM) is the most aggressive form of skin cancer, with increasing incidence worldwide. To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for ...MM. Our data highlight the potential of metabolomic characterization of cancer stem cell‐ or serum‐derived exosomes using high‐resolution mass spectrometry for the discovery of clinically useful MM biomarkers.
Malignant melanoma (MM) is the most aggressive and life‐threatening form of skin cancer. It is characterized by an extraordinary metastasis capacity and chemotherapy resistance, mainly due to melanoma cancer stem cells (CSCs). To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for this neoplasia. Therefore, there is an urgent need for new MM biomarkers that enable early diagnosis and effective disease monitoring. Exosomes represent a novel source of biomarkers since they can be easily isolated from different body fluids. In this work, a primary patient‐derived MM cell line enriched in CSCs was characterized by assessing the expression of specific markers and their stem‐like properties. Exosomes derived from CSCs and serums from patients with MM were characterized, and their metabolomic profile was analysed by high‐resolution mass spectrometry (HRMS) following an untargeted approach and applying univariate and multivariate statistical analyses. The aim of this study was to search potential biomarkers for the diagnosis of this disease. Our results showed significant metabolomic differences in exosomes derived from MM CSCs compared with those from differentiated tumour cells and also in serum‐derived exosomes from patients with MM compared to those from healthy controls. Interestingly, we identified similarities between structural lipids differentially expressed in CSC‐derived exosomes and those derived from patients with MM such as the glycerophosphocholine PC 16:0/0:0. To our knowledge, this is the first metabolomic‐based study aimed at characterizing exosomes derived from melanoma CSCs and patients' serum in order to identify potential biomarkers for MM diagnosis. We conclude that metabolomic characterization of CSC‐derived exosomes sets an open door to the discovery of clinically useful biomarkers in this neoplasia.
The current COVID-19 pandemic has overloaded the diagnostic capacity of laboratories by the gold standard method rRT-PCR. This disease has a high spread rate and almost a quarter of infected ...individuals never develop symptoms. In this scenario, active surveillance is crucial to stop the virus propagation.
Between July 2020 and April 2021, 11,580 oropharyngeal swab samples collected in closed and semi-closed institutions were processed for SARS-CoV-2 detection in pools, implementing this strategy for the first time in Córdoba, Argentina. Five-sample pools were constituted before nucleic acid extraction and amplification by rRT-PCR. Comparative analysis of cycle threshold (Ct) values from positive pools and individual samples along with a cost-benefit report of the whole performance of the results was performed.
From 2,314 5-sample pools tested, 158 were classified as positive (6.8%), 2,024 as negative (87.5%), and 132 were categorized as indeterminate (5.7%). The Ct value shift due to sample dilution showed an increase in Ct of 2.6±1.53 cycles for N gene and 2.6±1.78 for ORF1ab gene. Overall, 290 pools were disassembled and 1,450 swabs were analyzed individually. This strategy allowed correctly identifying 99.8% of the samples as positive (7.6%) or negative (92.2%), avoiding the execution of 7,806 rRT-PCR reactions which represents a cost saving of 67.5%.
This study demonstrates the feasibility of pooling samples to increase the number of tests performed, helping to maximize molecular diagnostic resources and reducing the work overload of specialized personnel during active surveillance of the COVID-19 pandemic.
The objective of this study was to determine the effect of bedrock, mean annual precipitation and slope orientation on soil organic carbon (SOC) accumulation of
Quercus pyrenaica Willd forests. ...Twelve different oak stands, along a rainfall gradient over two bedrock types (granites and schists), were selected for this study. Properties of the diagnostic soil horizons were determined. Bedrock type was the principal factor affecting soil development and fertility. Accumulated SOC varied between 33 and 185 Mg C ha
−
1
, the amounts of C accumulated over schists being significantly higher than over granites because of higher soil acidity, ‘silt
+
clay’ content and metal complexation. The SOC content in the entire profile was over 125 times higher than the C accumulated in the stand forest litter at the schist sites and 50 times higher at the granite sites. Soil acidity and metal complexation hampered microbial decomposition of soil organic matter, producing SOC accumulation and forming thick
umbric Ah/AB-horizons, being thicker at sites with high values of mean annual precipitation than at sites with low ones. Mineral N release was low in these soils.
Glutamine synthetase (GS) is a key enzyme in nitrogen metabolism, and the target of the herbicide phosphinothricin (PPT). Overexpression of cytosolic GS enhances the tolerance of poplar to PPT. ...Increases in GS, large subunit of Rubisco (LSU), and NADP+-isocitrate dehydrogenase (IDH) levels could be considered as mechanisms operating in young poplar leaves to overcome the toxic effect of PPT.
Glutamine synthetase (GS) is the main enzyme involved in ammonia assimilation in plants and is the target of phosphinothricin (PPT), an herbicide commonly used for weed control in agriculture. As a result of the inhibition of GS, PPT also blocks photorespiration, resulting in the depletion of leaf amino acid pools leading to the plant death. Hybrid transgenic poplar (
Populus tremula ×
P. alba INRA clone 7171-B4) overexpressing cytosolic GS is characterized by enhanced vegetative growth Gallardo, F., Fu, J., Cantón, F.R., García-Gutiérrez, A., Cánovas, F.M., Kirby, E.G., 1999. Expression of a conifer glutamine synthetase gene in transgenic poplar. Planta 210, 19–26; Fu, J., Sampalo, R., Gallardo, F., Cánovas, F.M., Kirby, E.G., 2003. Assembly of a cytosolic pine glutamine synthetase holoenzyme in leaves of transgenic poplar leads to enhanced vegetative growth in young plants. Plant Cell Environ. 26, 411–418; Jing, Z.P., Gallardo, F., Pascual, M.B., Sampalo, R., Romero, J., Torres de Navarra, A., Cánovas, F.M., 2004. Improved growth in a field trial of transgenic hybrid poplar overexpressing glutamine synthetase. New Phytol. 164, 137–145, increased photosynthetic and photorespiratory capacities El-Khatib, R.T., Hamerlynck, E.P., Gallardo, F., Kirby, E.G., 2004. Transgenic poplar characterized by ectopic expression of a pine cytosolic glutamine syntetase gene exhibits enhanced tolerance to water stress. Tree Physiol. 24, 729–736, enhanced tolerance to water stress (El-Khatib et al., 2004), and enhanced nitrogen use efficiency Man, H.-M., Boriel, R., El-Khatib, R.T., Kirby, E.G., 2005. Characterization of transgenic poplar with ectopic expression of pine cytosolic glutamine synthetase under conditions of varying nitrogen availability. New Phytol. 167, 31–39.
In vitro plantlets of GS transgenic poplar exhibited enhanced resistance to PPT when compared with non-transgenic controls. After 30
days exposure to PPT at an equivalent dose of 275
g
ha
−1, growth of GS transgenic poplar plantlets was 5-fold greater than controls. The response of young leaves to PPT treatment depends on physiological state as indicated by GS and Rubisco (LSU) levels. Young leaves from control plants, typically in a low differentiation state, respond to the herbicide showing up-regulation of GS and LSU. In contrast, young leaves from transgenic lines, with higher initial GS and LSU levels compared to control, display up-regulation of NADP
+-isocitrate dehydrogenase. Differences between control and GS transgenics in their response to PPT are discussed in relation to their differences in photosynthetic and photorespiratory capacities (
El-Khatib et al., 2004).
The main objective of this study was to know the soil P availability in
Quercus pyrenaica (deciduous oak) forests at the “
Sierra de Gata” Mountains (Central Western Spain) and determine the factors ...controlling the availability of P in these soils. Twelve different oak stands along a rainfall gradient were selected, differentiating underlying geological materials: granites and schist-greywackes. Samples from selected soil horizons were taken and the available soil P was determined using an anion exchange membrane (
P
AEM). P retention capacity (
P
RC) was used as a rapid measure of soil P adsorption. P mineralization rate and acid phosphatase activity (APA) were determined in samples of the epipedons. Sites developed over schist-greywacke materials showed significantly lower contents of
P
AEM than sites over granites. Soil
P
RC was related positively to the contents of organically complexed Al
+
Fe and negatively to
P
AEM contents, confirming that metal–organic complexes play an important role in the solubility and availability of soil P. The APA did not show any direct relationship neither with the net P mineralization rate nor with
P
AEM, but did with the soil organic carbon (SOC) content. P mineralization did not only depend on the biochemical mineralization, but also on the biological mineralization of SOC by heterotrophic micro-organisms, which activity is favoured by the SOC content.
Introduction
Inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) is a rare poor prognosis cytogenetic abnormality present in acute myeloid leukemia (AML) and other myeloid neoplasms.
Objective
The aim of this ...study was to evaluate the outcome of a cohort of 61 patients with newly diagnosed AML with inv(3)/t(3;3) treated with homogeneous intensive chemotherapy protocols conducted by the Spanish PETHEMA and CETLAM cooperative groups between 1999 and 2017.
Methods
In this retrospective study the main clinical and biologic parameters were collected. The complete response (CR) rate, the cumulative incidence of relapse (CIR) and the overall survival (OS) were calculated. An analysis of prognostic factors for survival was performed.
Results
Sixty‐one patients received induction and only 18 (29%) achieved CR (median age, 46 years). Allogeneic hematopoietic stem cell transplantation (alloHSCT) was performed in 36 patients (59%), 15 with active disease. One‐ and 4‐year CIR were 52% and 56%. One‐ and 4‐year OS probabilities were 41% and 13%. By multivariate analysis monosomal karyotype (MK) was associated with poorer OS (HR 2.0, P = .017).
Conclusion
Inv(3)/t(3;3) AML is a poor prognosis entity with low response to standard chemotherapy and to alloHSCT because of frequent and early relapse. MK was associated with a poorer prognosis. Improved therapeutic strategies are clearly needed.
A model for GABA synthesis in stems of pine seedlings is proposed. The localization of GABA in differentiating tracheids suggests a link between GABA production and vascular development. ...γ-aminobutyric acid (GABA) is a non-proteinogenic amino acid present in both prokaryotic and eukaryotic organisms. GABA plays a fundamental role as a signal molecule in the central nervous system in animals. In plants, GABA has been correlated with cellular elongation, plant development, gene expression regulation, synthesis of ethylene and other hormones, and signaling. Considering the physiological importance of GABA in plants, the lack of works about GABA localization in this kingdom seems surprising. In this work, the immunolocalization of GABA in root and hypocotyl during seedling development and in bent stem showing compression xylem has been studied. In the seedling root, the GABA signal was very high and restricted to the stele supporting previous evidences indicating a potential role for this amino acid in root growth and nutrient transport. In hypocotyl, GABA was localized in vascular tissues, including differentiating xylem, ray parenchyma and epithelial resin duct cells, drawing also a role for GABA in vascular development, communication and defense. During the production of compression wood, a special lignified wood produced when the stem loss its vertical position, a clear GABA signal was found in the new differentiating xylem cells showing a gradient-like pattern with higher signal in less differentiated elements. The results are in accordance with a previous work indicating that glutamate decarboxylase and GABA production are associated to vascular differentiation in pine Molina-Rueda et al. (Planta 232: 1471-1483, 2010 ). A model for GABA synthesis in vascular differentiation, communication, and defense is proposed in the stem of pine seedlings.PUBLICATION ABSTRACT Erratum DOI: 10.1007/s00425-014-2188-x
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![A putative role for [gamma]...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0032-0935/small "A putative role for [gamma]-aminobutyric acid (GABA) in vascular development in pine seedlings")
